Our results using AQX-435 demonstrate that SHIP1 activation may be an effective novel therapeutic strategy for treatment of B-cell neoplasms, alone or in combination with ibrutinib.
Systemic delivery of SHIP1-TK/GCV in PDAC xenograft mice significantly suppressed PANC-1 tumor growth in vivo greater than RIP-TK/GCV and CMV-TK/GCV controls (p < .05).
The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis.
Recent studies have shown that beyond "canonical" turnover by the PIP<sub>3</sub> phosphatases and tumor suppressors phosphatase and tensin homolog (PTEN) and SH2 domain-containing inositol-5-phosphatase-1 (SHIP-1/2), PIP<sub>3</sub> function in hematopoietic cells can also be dampened through antagonism with the soluble PIP<sub>3</sub> analogs inositol(1,3,4,5)tetrakisphosphate (IP<sub>4</sub>) and inositol-heptakisphosphate (IP<sub>7</sub>).
These results indicate that SHIP1 can act as a tumor suppressor in acute myeloid leukemia cells and that higher SHIP1 expression is associated with prolonged overall survival in AML patients.
Collectively, these results establish the tumour suppressive role of phosphatidylinositol 4,5-bisphosphate 5-phosphatase and reveal mechanisms involved in its downregulation in melanoma.
To evaluate the possible tumor suppressor role of the SHIP gene in myeloid leukemogenesis, we examined primary leukemia cells from 30 acute myeloid leukemia (AML) patients, together with eight myeloid leukemia cell lines.